Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026
Anti-Methicillin-Resistant Staphylococcus aureus (MRSA) Cephalosporins Plus Daptomycin as Initial Therapy for MRSA Bacteremia: Does a "Hit Hard and Fast" Strategy Improve Outcomes?
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Bavaro Davide Fiore, Belati Alessandra, Sacchet Davide, Cilli Alessandro, Diella Lucia, Pocaterra Daria, Casana Maddalena, Barbanotti Diletta, Morelli Paola, Frallonardo Luisa, Di Gennaro Francesco, Ronga Luigi, Bollini Riccardo, Scuderi Cristina, Casari Erminia, Cento Valeria, Bussini Linda, Patrucco Carolina, Pascale Renato, Saracino Annalisa, Berna Giovanni, Carbonara Sergio, Giannella Maddalena, Viale Pierluigi, Bartoletti Michele
Аннотация
BACKGROUND: The study aim was to evaluate the effectiveness of anti-methicillin-resistant Staphylococcus aureus (MRSA) cephalosporins in combination with daptomycin (anti-MRSA Ceph + DAP) compared to other antimicrobial regimens (OARs) as initial treatment of MRSA bloodstream infection (BSI).
METHODS: This retrospective observational study enrolled patients with MRSA-BSI from 1 January 2020 to 31 December 2024 at 4 large Italian hospitals. The primary endpoint was 90-day all-cause mortality. Cox regression was used for primary endpoint analysis; results were confirmed with inverse probability of treatment weighting (IPTW). Treatment efficacy was also assessed using the desirability of outcome ranking (DOOR) approach, assigning 1 additional point beyond recovery for 1 of the following negative outcomes: (i) persistent MRSA infection, (ii) persistent bacteremia (≥5 days), (iii) drug resistance, (iv) any adverse event, and (v) 90-day relapse. A score of 7 was assigned for death at any time point.
RESULTS: Overall, 465 patients were enrolled: Median age was 76 (IQR, 61-83) years, 59% male, with a Charlson Comorbidity Index score of 7 (IQR, 4-8). Of them, 50 (11%) and 116 (25%) patients had endocarditis and metastatic infection, respectively. Importantly, 90-day mortality occurred in 181 (39%) patients, while 260 (56%) experienced at least 1 negative outcome included in DOOR analysis. Overall, patients in the anti-MRSA Ceph + DAP arm had a 59.9% (95% CI, 52.4%-67.4%) probability of having a better outcome than those in the OAR arm. Particularly, anti-MRSA Ceph + DAP was associated with reduced mortality (aHR, 0.54 [95% CI, .34-.85]), confirmed after adjustment with IPTW analysis.
CONCLUSIONS: Anti-MRSA Ceph + DAP could represent a valid initial therapy for MRSA-BSI, especially in patients with high risk of worse outcomes.
METHODS: This retrospective observational study enrolled patients with MRSA-BSI from 1 January 2020 to 31 December 2024 at 4 large Italian hospitals. The primary endpoint was 90-day all-cause mortality. Cox regression was used for primary endpoint analysis; results were confirmed with inverse probability of treatment weighting (IPTW). Treatment efficacy was also assessed using the desirability of outcome ranking (DOOR) approach, assigning 1 additional point beyond recovery for 1 of the following negative outcomes: (i) persistent MRSA infection, (ii) persistent bacteremia (≥5 days), (iii) drug resistance, (iv) any adverse event, and (v) 90-day relapse. A score of 7 was assigned for death at any time point.
RESULTS: Overall, 465 patients were enrolled: Median age was 76 (IQR, 61-83) years, 59% male, with a Charlson Comorbidity Index score of 7 (IQR, 4-8). Of them, 50 (11%) and 116 (25%) patients had endocarditis and metastatic infection, respectively. Importantly, 90-day mortality occurred in 181 (39%) patients, while 260 (56%) experienced at least 1 negative outcome included in DOOR analysis. Overall, patients in the anti-MRSA Ceph + DAP arm had a 59.9% (95% CI, 52.4%-67.4%) probability of having a better outcome than those in the OAR arm. Particularly, anti-MRSA Ceph + DAP was associated with reduced mortality (aHR, 0.54 [95% CI, .34-.85]), confirmed after adjustment with IPTW analysis.
CONCLUSIONS: Anti-MRSA Ceph + DAP could represent a valid initial therapy for MRSA-BSI, especially in patients with high risk of worse outcomes.